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Molecular and Cellular Biology

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https://www.readbyqxmd.com/read/28716951/a-calcium-diacylglycerol-stimulated-protein-kinase-c-c-elegans-pkc-2-links-thermal-signals-to-learned-behavior-by-acting-in-a-sensory-neuron-and-intestinal-cells
#1
Marianne Land, Charles S Rubin
Ca(2+) and diacylglycerol (DAG) activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a C. elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc) and migrates along Tc within a 17-25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28716950/analysis-of-small-critical-regions-of-swi1-conferring-prion-formation-maintenance-and-transmission
#2
Stephanie Valtierra, Zhiqiang Du, Liming Li
Saccharomyces cerevisiae contains several prion elements, which are epigenetically transmitted as self-perpetuating protein conformations. One such prion is [SWI(+) ], whose protein determinant is Swi1, a subunit of the SWI/SNF chromatin-remodeling complex. We previously reported that [SWI(+) ] formation results in a partial loss-of-function phenotype of poor growth in non-glucose media and abolishment of multicellularity. We also showed that the first 38 amino acids of Swi1 propagated [SWI(+)]. We show here that a region as small as the first 32 amino acids of Swi1 (Swi11-32) can decorate [SWI(+)] aggregation and stably maintain and transmit [SWI(+)] independently of full-length Swi1...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28716949/biochemical-regulatory-features-of-aid-remain-conserved-from-lamprey-to-humans
#3
Emma M Quinlan, Justin J King, Chris T Amemiya, Ellen Hsu, Mani Larijani
Activation induced cytidine deaminase (AID) is a genome-mutating enzyme that initiates class switch recombination and somatic hypermutation of antibodies in jawed vertebrates. We previously described the biochemical properties of human AID and found that it is an unusual enzyme in that it exhibits binding affinities for its substrate DNA and catalytic rates several orders of magnitude higher and lower, respectively, than a typical enzyme. Recently, we solved the functional structure of AID and demonstrated that these properties are due to non-specific DNA binding on its surface, along with a catalytic pocket that predominantly assumes a closed conformation...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28716948/cooperative-repression-of-igf2r-translation-by-mir-195-and-rna-binding-protein-cugbp1
#4
Yuan Zhang, Yun Zhang, Lan Xiao, Ting-Xi Yu, Jun-Zhe Li, Jaladanki N Rao, Douglas J Turner, Myriam Gorospe, Jian-Ying Wang
Insulin-like growth factor type-2 (IGF2) receptor (IGF2R) recognizes mannose 6-phosphate-containing molecules and IGF2 and plays an important role in many pathophysiological processes including gut mucosal adaptation. However, the mechanisms that control cellular IGF2R abundance are poorly known. MicroRNAs (miRNAs) and RNA-binding proteins (RBP) critically regulate gene expression programs in mammalian cells by modulating the stability and translation of target mRNAs. Here we report that miRNA-195 (miR-195) and the RBP CUG-binding protein 1 (CUGBP1) jointly regulate IGF2R expression at the posttranscriptional level in intestinal epithelial cells...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28694333/epc1-tip60-mediated-histone-acetylation-facilitates-spermiogenesis-in-mice
#5
Yixin Dong, Kyo-Ichi Isono, Kazuyuki Ohbo, Takaho A Endo, Osamu Ohara, Mamiko Maekawa, Yoshiro Toyama, Chizuru Ito, Kiyotaka Toshimori, Kristian Helin, Narumi Ogonuki, Kimiko Inoue, Atsuo Ogura, Kazutsune Yamagata, Issay Kitabayashi, Haruhiko Koseki
Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian Nucleosome acetyltransferase of H4 (NuA4) complexes, are co-expressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28694332/the-ets2-repressor-factor-erf-is-required-for-effective-primitive-and-definitive-hematopoiesis
#6
Ioanna Peraki, James Palis, George Mavrothalassitis
Erf is a ubiquitously expressed ets-DNA-binding containing transcriptional repressor. Erf haploinsufficiency causes craniosynostosis in human and mice, while its absence in mice leads to failed chorioallantoic fusion and death at E10.5. In this study, we show that Erf is required in all three waves of embryonic hematopoiesis. Mice lacking Erf in embryo proper exhibited severe anemia and died around embryonic day (E) 14.5. Erf epiblast specific knockout embryos had reduced numbers of circulating blood cells from E9...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28694331/transcriptional-elongation-control-of-the-hbv-cccdna-transcription-by-super-elongation-complex-sec-and-brd4
#7
Joel Celio Francisco, Qian Dai, Zhuojuan Luo, Yan Wang, Roxanne Hui-Heng Chong, Yee Joo Tan, Wei Xie, Guan-Huei Lee, Chengqi Lin
Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. HBV reactivation during or after chemotherapy is a potentially fatal complication for cancer patients with chronic HBV infection. Transcription of HBV is a critical intermediate step of HBV life cycle. However, factors controlling the HBV transcription remain largely unknown. Here, we found that different P-TEFb complexes are involved in the transcription of the HBV viral genome. Both BRD4 and the Super Elongation Complex (SEC) bind to the HBV genome...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28694330/phosphorylation-of-the-c-raf-n-region-promotes-raf-dimerization
#8
Maho Takahashi, Yanping Li, Tara J Dillon, Yumi Kariya, Philip J S Stork
Activation of Raf kinases by the small GTPase Ras requires two major sets of phosphorylations. One set lies within the activation loop and the other lies within the N-terminal acidic region (N-region). In the most abundant isoform of Raf, C-Raf, N-region phosphorylations occur on serine 338 (S338) and tyrosine 341 (Y341), and are thought to provide allosteric activation of the Raf dimer. We show that the phosphorylation of these N-region sites does not require C-Raf dimerization, but rather, they precede dimerization...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28694329/feminization-of-male-mouse-liver-by-persistent-growth-hormone-stimulation-activation-of-sex-biased-transcriptional-networks-and-dynamic-changes-in-chromatin-states
#9
Dana Lau-Corona, Alexander Suvorov, David J Waxman
Sex-dependent pituitary GH secretory profiles--pulsatile in males and persistent in females--regulate sex-biased, STAT5-dependent expression of hundreds of genes in mouse liver, imparting sex differences in hepatic drug/lipid metabolism and disease risk. Here we examine transcriptional and epigenetic changes induced by continuous-GH infusion (cGH) in male mice, which rapidly feminizes the temporal profile of liver STAT5 activity. cGH repressed 86% of male-biased genes and induced 68% of female-biased genes within 4-days; however, several highly female-specific genes showed weak or no feminization, even after 14-days cGH...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28674188/nrf2-activation-impairs-quiescence-and-bone-marrow-reconstitution-capacity-of-hematopoietic-stem-cells
#10
Shohei Murakami, Takuma Suzuki, Hideo Harigae, Paul-Henri Romeo, Masayuki Yamamoto, Hozumi Motohashi
Tissue stem cells are maintained in quiescence under physiological conditions but proliferate and differentiate to replenish mature cells under stressed conditions. The KEAP1-NRF2 system plays an essential role in the stress response and cytoprotection against redox disturbance. To clarify the role of the KEAP1-NRF2 system in tissue stem cells, we focused on hematopoiesis in this study and examined the effects of persistent activation of NRF2 on long-term hematopoietic stem cells (LT-HSCs) using Keap1-deficient mice...
July 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28674187/pras40-connects-microenvironmental-stress-signaling-to-exosome-mediated-secretion
#11
Jiacong Guo, Priya Jayaprakash, Jian Dan, Petra Wise, Gyu-Beom Jang, Chengyu Liang, Mei Chen, David T Woodley, Muller Fabbri, Wei Li
Secreted exosomes carrying lipids, proteins and nucleic acids conduct cell-cell communications within the microenvironment of both physiological and pathological conditions. Exosome secretion is triggered by extracellular or intracellular stress signals. Little is known, however, about the signal transduction between stress cues and exosome secretion. To identify the linker protein, we took advantage of a unique finding in human keratinocytes. In these cells, although TGFα and EGF share the same EGF receptor and previously indistinguishable intracellular signaling networks, only TGFα stimulation causes exosome-mediated secretion...
July 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28674186/tgf%C3%AE-nr4a1-inducible-breast-cancer-cell-migration-and-epithelial-to-mesenchymal-transition-is-p38%C3%AE-mapk14-dependent
#12
Erik Hedrick, Stephen Safe
Transforming growth factor β (TGFβ)-induced migration of triple negative breast cancer (TNBC) cells is dependent on nuclear export of the orphan receptor NR4A1 which plays a role in proteasome-dependent degradation of SMAD7. In this study, we show that TGFβ induces p38α (MAPK14) which in turn phosphorylates NR4A1, resulting in nuclear export of the receptor. TGFβ/p38α and NR4A1 also play essential roles in the induction of epithelial to mesenchymal transition (EMT) and induction of β-catenin in TNBC cells, and these TGFβ-induced responses and nuclear export of NR4A1 are blocked by NR4A1 antagonists, the p38 inhibitor SB202190, kinase dead [p38(KD)] and dominant negative [p38(DN)] forms of p38α...
July 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28674185/yeast-rna-binding-protein-nab3-regulates-genes-involved-in-nitrogen-metabolism
#13
Jonathan Merran, Jeffry L Corden
Termination of yeast RNA polymerase II (Pol II) transcripts occurs through two alternative pathways. Termination of mRNAs is coupled to cleavage and polyadenylation while non-coding transcripts are terminated through the Nrd1-Nab3-Sen1 (NNS) pathway in a process that is linked to RNA degradation by the nuclear exosome. Some mRNA transcripts are also attenuated through premature termination directed by the NNS complex. In this paper we present the results of nuclear depletion of the NNS component Nab3. As expected many non-coding RNAs fail to terminate properly...
July 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28674184/steady-state-levels-of-phosphorylated-mitogen-activated-protein-kinase-kinase-1-2-determined-by-mortalin-hspa9-and-protein-phosphatase-1-alpha-in-kras-and-braf-tumor-cells
#14
Pui-Kei Wu, Seung-Keun Hong, Jong-In Park
Although deregulation of MEK/ERK activity is a key feature in cancer, high magnitude MEK/ERK activity can paradoxically induce growth inhibition. Therefore, additional mechanisms may exist to modulate MEK/ERK activity in favor of tumor cell proliferation. We previously reported that mortalin/HSPA9 can facilitate proliferation of certain KRAS- and BRAF-tumor cells by modulating MEK/ERK activity. In this study, we demonstrate that mortalin can regulate MEK/ERK activity via protein phosphatase 1α (PP1α). We found that PP1α inhibition increases steady-state levels of phosphorylated MEK1/2 in various tumor cells expressing B-Raf(V600E) or K-Ras(G12D/V) Intriguingly, co-immunoprecipitation and in vitro binding assays revealed that mortalin facilitates PP1α-mediated MEK1/2 dephosphorylation by promoting PP1α-MEK1/2 interaction in an ATP-sensitive manner...
July 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28674183/n-terminal-part-of-dishevelled-dep-domain-is-required-for-wnt-%C3%AE-catenin-signaling-in-mammalian-cells
#15
Petra Paclíková, Ondřej Bernatík, Tomasz Witold Radaszkiewicz, Vítězslav Bryja
Dishevelled (DVL) proteins are key mediators of Wnt/β-catenin signaling pathway. All DVL proteins contain three conserved domains -- DIX, PDZ and DEP. There is a consensus in the field that DIX domain is critical for Wnt/β-catenin signaling but contradictory evidence exists regarding the function of the DEP domain. It has been difficult until recently to test the importance of the DEP domain rigorously because of the interference with endogenous DVL, expressed in all Wnt-responsive cell lines. In this study, we took advantage of DVL KO (DVL1/DVL2/DVL3-triple knockout) cells, fully deficient in Wnt3a-induced signaling events, and performed series of rescue experiments...
July 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28652267/mammalian-ecd-protein-is-a-novel-negative-regulator-of-the-perk-arm-of-unfolded-protein-response
#16
Appolinaire A Olou, Aniruddha Sarkar, Aditya Bele, C B Gurumurthy, Riyaz A Mir, Shalis A Ammons, Sameer Mirza, Irfana Saleem, Fumihiko Urano, Hamid Band, Vimla Band
The mammalian Ecdysoneless (ECD) is a highly-conserved ortholog of the Drosophila Ecd gene product whose mutations impair the synthesis of Ecdysone and produce cell-autonomous survival defects but mechanisms by which ECD functions are largely unknown. Here, we present evidence that ECD regulates endoplasmic reticulum (ER) stress response. ER stress induction led to a reduced ECD protein but this effect was not seen in PERK KO or phospho-deficient eIF2α MEFs; moreover, ECD mRNA levels were increased, suggesting impaired ECD translation as the mechanism for reduced protein levels...
June 26, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28652266/long-non-coding-rna-jhdm1d-as1-promotes-tumor-growth-by-regulating-angiogenesis-in-response-to-nutrient-starvation
#17
Ayano Kondo, Aya Nonaka, Teppei Shimamura, Shogo Yamamoto, Tetsuo Yoshida, Tatsuhiko Kodama, Hiroyuki Aburatani, Tsuyoshi Osawa
Long non-coding RNAs play a pivotal role in tumor progression, but their role in cancer cells in the nutrient-starved tumor microenvironment remains unknown. Here, we show that a nutrient starvation-responsive long non-coding RNA, JHDM1D antisense 1 (JHDM1D-AS1), promotes tumorigenesis by regulating angiogenesis in response to nutrient starvation. Expression of JHDM1D-AS1 was increased in cancer cells. In addition, expression of JHDM1D-AS1 was increased in clinical tumor samples compared to that in normal tissue...
June 26, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28630282/desumoylation-of-gli1-by-senp1-attenuates-sonic-hedgehog-signaling
#18
Huaize Liu, Sen Yan, Jie Ding, Ting-Ting Yu, Steven Y Cheng
Transcriptional output of the Sonic hedgehog morphogenic pathway is orchestrated by three Krüppel family transcription factors, Gli1-3, which undergo extensive post-translational modifications, including ubiquitination and SUMOylation. Here, we report that sentrin-specific peptidase SENP1 is the specific de-SUMOylation enzyme for Gli1. We show that SUMOylation stabilizes Gli1 by competing with ubiquitination at conserved lysine residues, and SUMOylated Gli1 is enriched in the nucleus, suggesting that SUMOylation is a nuclear localization signal for Gli1...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28630281/evidence-of-a-prion-like-transmission-of-p53-amyloid-in-saccharomyces-cerevisiae
#19
Shinjinee Sengupta, Samir K Maji, Santanu K Ghosh
Loss of p53 function is largely responsible for the occurrence of cancer in human. Aggregation of mutant p53 has been found in multiple cancer cell types suggesting a role of aggregation for loss of p53 function and cancer development. The p53 protein has recently been hypothesized to possess a prion-like conformation although experimental evidence is lacking. Here, we report that human p53 can be inactivated upon exposure to preformed fibrils containing an aggregation prone sequence specific peptide PILTIITL derived from p53 and the inactive state was found to be stable for many generations...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28630280/ki-67-contributes-to-normal-cell-cycle-progression-and-inactive-x-heterochromatin-in-p21-checkpoint-proficient-human-cells
#20
Xiaoming Sun, Aizhan Bizhanova, Timothy D Matheson, Jun Yu, Julie L Zhu, Paul D Kaufman
Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here, we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by co-depletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of cell cycle inhibitor p21...
June 19, 2017: Molecular and Cellular Biology
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